Citius Pharmaceuticals and Citius Oncology have announced encouraging preliminary results from an ongoing Phase 1 clinical trial evaluating the combination of pembrolizumab (Keytruda) and LYMPHIR (denileukin diftitox-cxdl or E7777) in patients with recurrent solid tumors. The trial, focusing on gynecological malignancies, is nearing completion, with only three subjects remaining to be enrolled.
The data, presented at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting, revealed a 27% objective response rate (ORR) and a 33% clinical benefit rate (CBR) among evaluable patients. Notably, the median progression-free survival (PFS) for patients achieving clinical benefit was 57 weeks.
Promising Efficacy Data
The Phase 1 trial enrolled 21 patients with recurrent or metastatic solid tumors. Of the 15 evaluable patients, 4 achieved a partial response, and 1 demonstrated durable stable disease lasting over six months. The combination regimen was generally well-tolerated, with most adverse events related to the patients' underlying disease. Importantly, no significant immune-related adverse events were observed, and only one case of dose-limiting toxicity (capillary leak syndrome) was reported at the highest dose level (12 mcg/kg).
"We have seen promising results in patients with heavily pre-treated recurrent or metastatic gynecologic tumors," said Dr. Haider Mahdi, Assistant Professor at the University of Pittsburgh, who is conducting the trial. He added that further investigation will explore the therapy's impact on Tregs, host immune-effector cells, and the tumor microenvironment.
Rationale for Combination Therapy
The rationale behind combining LYMPHIR with pembrolizumab lies in LYMPHIR's ability to deplete immunosuppressive regulatory T lymphocytes (Tregs) within the tumor microenvironment. Pembrolizumab, a PD-1 inhibitor, works by blocking the PD-1 protein on T cells, enabling the immune system to recognize and attack cancer cells. By temporarily depleting Tregs, LYMPHIR may enhance pembrolizumab's anti-tumor activity without triggering an autoimmune response.
Dr. Myron Czuczman, Chief Medical Officer of Citius Pharmaceuticals and Citius Oncology, stated, "This efficacy data strongly suggests that LYMPHIR may have the ability to improve and prolong the anti-tumor activity of immune checkpoint inhibitors... To date, this unique regimen has not been associated with significant immune-related adverse events."
Trial Design and Patient Population
The open-label, dose-escalation Phase 1 trial evaluated the safety and preliminary efficacy of pembrolizumab in combination with LYMPHIR in patients with recurrent or metastatic solid tumors. LYMPHIR was administered at four dose levels (3, 6, 9, and 12 mcg/kg) in combination with pembrolizumab (200 mg) on a 21-day cycle for eight cycles, followed by pembrolizumab monotherapy as maintenance. The trial enrolled patients with various solid tumors, including ovarian, endometrial, and cervical cancers.
LYMPHIR: A Targeted Immunotherapy
LYMPHIR is a targeted immune therapy approved by the FDA for relapsed or refractory cutaneous T-cell lymphoma (CTCL). It is a recombinant fusion protein that combines the IL-2 receptor binding domain with diphtheria toxin fragments, causing cell death in IL-2R-expressing tumors. Citius Oncology estimates the initial market for LYMPHIR currently exceeds $400 million.
Next Steps
Citius Oncology plans to expand research into a Phase 2 study to further evaluate the combination's benefits across a broader range of solid tumor types. The company believes the positive signals from the Phase 1 data support this expansion.
